| Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7. | |
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MedLine Citation:
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PMID: 20300600 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells. |
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Authors:
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Rebecca Phillips; Mattias Svensson; Naveed Aziz; Asher Maroof; Najmeeyah Brown; Lynette Beattie; Nathalie Signoret; Paul M Kaye |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-12 |
Journal Detail:
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Title: PLoS pathogens Volume: 6 ISSN: 1553-7374 ISO Abbreviation: PLoS Pathog. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-19 Completed Date: 2010-06-24 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 101238921 Medline TA: PLoS Pathog Country: United States |
Other Details:
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Languages: eng Pagination: e1000813 Citation Subset: IM |
Affiliation:
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Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Gene Expression / immunology Interferon Regulatory Factor-7 / genetics, immunology*, metabolism Interferon-alpha / immunology, metabolism Interferon-gamma / immunology, metabolism Leishmania donovani / immunology* Leishmaniasis, Visceral / immunology* Macrophages / cytology, immunology*, parasitology* Mice Mice, Inbred C57BL Nitric Oxide / metabolism Phagosomes / immunology RNA, Small Interfering Spleen / immunology, parasitology |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Interferon Regulatory Factor-7; 0/Interferon-alpha; 0/Irf7 protein, mouse; 0/RNA, Small Interfering; 10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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